Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation

Exposure to ionizing radiation during childhood is a well-known risk factor for thyroid cancer. Our study evaluated the effect of age on the radiosensitivity of rat thyroid glands. Four-week-old (4W), 7 -week-old (7W), and 8-month-old (8M) male Wistar rats were exposed to 8 Gy of whole-body X-ray irradiation. Thyroids were removed 3–72 h after irradiation, and non-irradiated thyroids served as controls. Ki67-positivity and p53 binding protein 1 (53BP1) focus formation (a DNA damage response) were evaluated via immunohistochemistry. Amounts of proteins involved in DNA damage response (p53, p53 phosphorylated at serine 15, p21), apoptosis (cleaved caspase-3), and autophagy (LC3, p62) were determined via western blotting. mRNA levels of 84 key autophagy-related genes were quantified using polymerase chain reaction arrays. Ki67-positive cells in 4W (with high proliferative activity) and 7W thyroids significantly decreased in number post-irradiation. The number of 53BP1 foci and amount of p53 phosphorylated at serine 15 increased 3 h after irradiation, regardless of age. No increase in apoptosis or in the levels of p53, p21 or cleaved caspase-3 was detected for any ages. Levels of LC3-II and p62 increased in irradiated 4W but not 8M thyroids, whereas expression of several autophagy-related genes was higher in 4W than 8M irradiated thyroids. Irradiation increased the expression of genes encoding pro-apoptotic proteins in both 4W and 8M thyroids. In summary, no apoptosis or p53 accumulation was noted, despite the expression of some pro-apoptotic genes in immature and adult thyroids. Irradiation induced autophagy in immature, but not in adult, rat thyroids.     

Lidocaine‐Propitocain Cream,a Eutectic Mixture of Local Anesthetics,Effectively Relieves Pain Associated With Vascular Access Intervention Therapy in Patients Undergoing Hemodialysis: A Placebo‐Controlled,Double‐Blind,Crossover Study

Vascular access intervention therapy (VAIVT) is necessary to maintain vascular access in patients undergoing hemodialysis. VAIVT‐associated vasodilatation is painful. However, few reports have focused on effective pain relief at the time of VAIVT. The present study was performed to determine whether lidocaine‐propitocain cream, a eutectic mixture of local anesthetics (EMLA), effectively reduces VAIVT‐associated pain in patients undergoing hemodialysis. This placebo‐controlled, double‐blind, crossover study was conducted in a single center. Among 210 patients who underwent a total of 437 VAIVT procedures from August 2017 to June 2018, 30 patients were randomly allocated to either the EMLA–placebo arm or placebo–EMLA arm at the time of VAIVT. EMLA application significantly reduced the visual analog scale score compared with placebo (47.0 ± 21.1 vs. 68.6 ± 20.7 mm, respectively; P < 0.05). EMLA is a safe and effective treatment for relief of VAIVT‐associated pain in patients undergoing hemodialysis.     

Protein-bound polysaccharide K induced apoptosis of the human Burkitt lymphoma cell line, Namalwa.

Protein-bound polysaccharide K (PSK), which is derived from mushrooms belonging to the Basidiomycetes genus, has been clinically used as a biological response modifier (BRM) for the treatment of epithelial cancer patients in Japan and other Asian countries. There are a large number of studies on the biological activities of PSK as regards the activation of immunocompetent cells and the potential cytotoxic effects on epithelial cancer cells. However, only a few studies have been conducted to see the direct cytotoxic effects of PSK on hematological malignant cells. In this study, we investigated whether or not PSK was able to induce cellular apoptosis in hematological malignant cells. PSK was found to inhibit cell growth, and induced subsequent cellular apoptosis in the Burkkit lymphoma cell line (Namalwa), out of 33 hematological malignant cell lines tested. This PSK-induced apoptosis was neutralized by the addition of galactose to the culture medium, whereas apoptosis was augmented by treatment with beta-galactosidase, indicating the inhibitory involvement of galactose in the mechanism of action. These results provide initial evidence of the direct cytotoxic activity of PSK in a hematological malignant cell line, thus encouraging further molecular-level study of PSK-mediated apoptosis in malignant hematological cells.     

Dextran Sulfate Sodium-Induced Colitis in Immunodeficient Rats

To examine the morphology of colitis and study the role of the immune system in colitis, we compared colitis in immunocompetent Wistar-Kyoto rats with that in spontaneously hypertensive rats, known to have T-cell dysfunction. Rats were treated with 3% dextran sulfate in drinking water for periods ranging from 3 to 60 days. Diarrhea developed earlier and was associated with a more severe weight loss in Wistar-Kyoto rats than spontaneously hypertensive rats. The morphologic findings (flattening of the gland epithelium, gland dropout and ulceration) in spontaneously hypertensive rats were milder than in Wistar-Kyoto rats. Only spontaneously hypertensive rats survived 60 days of treatment; the findings included ulceration, crypt distortion, and inflammatory pseudopolyp formation. Immunostaining for B-cell, T-cell, and macrophage markers showed no difference in the distribution of these cells in the mucosa of Wistar-Kyoto rats and spontaneously hypertensive rats. Spontaneously hypertensive rats with T-cell dysfunction develop dextran sulfate sodium-induced colitis.     

Ramatroban (BAY u 3405): A Novel Dual Antagonist of TXA2 Receptor and CRTh2, a Newly Identified Prostaglandin D2 Receptor

It is known that thromboxane A₂ (TXA₂) contributes to various diseases such as bronchial asthma, ischemic heart disease, cerebrovascular disorders and allergic rhinitis. A number of TXA₂ synthase inhibitors and TXA₂ receptor (TP receptor) antagonists have been developed to treat these diseases. Ramatroban (BAY u 3405) was developed as a potent TP receptor antagonist with excellent efficacy against allergic rhinitis in many animal models and patients. Recent studies also revealed that ramatroban can block the newly identified PGD₂ receptor, chemoattractant receptor‐homologous molecule expressed on Th2 cells (CRTh2). PGD₂ induces migration and degranulation of eosinophils through CRTh2 and contributes to late‐phase inflammation and cell damage. Accordingly, it was considered that ramatroban suppresses the late‐phase inflammation via TP receptor and CRTh2 blockade. In terms of the efficacy on vascular systems, it was revealed that ramatroban can suppress the expression of monocyte chemoattractant protein‐1 (MCP‐1) and adhesion molecules in endothelial cells and prevent exacerbation of inflammation by blocking these responses. According to our recent studies in hypercholesterolemic rabbits ramatroban prevents macrophage infiltration through MCP‐1 downregulation and neointimal formation after balloon injury and attenuates vascular response to acetylcholine. Therefore, ramatroban may be beneficial in the treatment of atherosclerosis.     

Role for interleukin-6 and insulin-like growth factor-I via PI3-K/Akt pathway in the proliferation of CD56- and CD56+ multiple myeloma cells

OBJECTIVES: Several studies including ours have suggested that lack of CD56 in multiple myeloma (MM) defines a unique patient subset with poorer prognosis. However, the mechanism underlying this aggressive behavior of CD56(-) MM has not been well elucidated. Interleukin-6 (IL-6) or insulin-like growth factor I (IGF-I) induce proliferation of MM cells. In this study, we report about the relationship between CD56 expression and responsiveness to these cytokines. METHODS: We sorted out both CD56(-) and CD56(+) fractions from MM cell lines such as KMS-21-BM and U-266, and investigated their different responsiveness to IL-6 or IGF-I. Furthermore, we compared the effects of these cytokines on the regulation of cell-cycle distribution between CD56(-) and CD56(+) cells. RESULTS: Although CD56(-) cells in both KMS-21-BM and U-266 cells responded significantly to IL-6, CD56(+) cells did not. Ki-67(+) cells in the CD56(-) cells were significantly increased by IL-6. Western blotting showed that IL-6 phosphorylated Akt, and upregulated and downregulated the level of cyclin D1 and p27 protein in the CD56(-) KMS-21-BM cells, respectively. LY-294002 completely blocked these effects of IL-6. On the other hand, Ki-67(+) cells in the CD56(+) cells did not respond to IL-6. Anti-IGF-I mAb significantly reduced Ki-67(+) cells only in the CD56(+) cells. IGF-I phosphorylated Akt and upregulated cyclin D1 in the CD56(+) KMS-21-BM cells, which was completely blocked by LY294002. CONCLUSIONS: These results suggest that CD56(-) and CD56(+) MM cells could be stimulated by IL-6 and IGF-I, respectively, via PI3-K/Akt pathway, and provide useful information for anticytokine therapies.     

Possible difficult laryngoscopy caused by masticatory muscle tendon-aponeurosis hyperplasia: we anesthesiologists should be aware of this disease

Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a new disease entity characterized by limited mouth opening due to contracture of the masticatory muscles resulting from hyperplasia of tendons and aponeuroses. The other clinical feature is that the face of the patient with this disease displays a square mandible configuration. Muscle relaxants provide no relief for the limited mouth-opening ability. Anesthesiologists need to suspect difficult airway when patients have limited mouth opening with square mandible configuration. MMTAH can therefore be a possible cause of difficult intubation.